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Wen-Yu Qian,1,* Dong-Mei Sun,1,* Rong-Rong Zhu,1 Xi-Ling Du,1 Hui Liu,2 Shi-Long Wang11Shanghai Tenth People's Hospital, School of Life Science and Technology, Tongji University, Shanghai, PR China; 2Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, PR China*Wen-Yu Qian and Dong-Mei Sun contributed equally to this workAbstract: Strontium carbonate nanoparticles (SCNs), a novel biodegradable nanosystem for the pH-sensitive release of anticancer drugs, were developed via a facile mixed solvent method aimed at creating smart drug delivery in acidic conditions, particularly in tumor environments. Structural characterization of SCNs revealed that the engineered nanocarriers were uniform in size and presented a dumbbell-shaped morphology with a dense mass of a scale-like spine coating, which could serve as the storage structure for hydrophobic drugs. Chosen as a model anticancer agent, etoposide was effectively loaded into SCNs based on a simultaneous process that allowed for the formation of the nanocarriers and for drug storage to be accomplished in a single step. The etoposide-loaded SCNs (ESCNs) possess both a high loading capacity and efficient encapsulation. It was found that the cumulative release of etoposide from ESCNs is acid-dependent, and that the release rate is slow at a pH of 7.4; this rate increases significantly at low pH levels (5.8, 3.0). Meanwhile, it was also found that the blank SCNs were almost nontoxic to normal cells, and ESCN systems were evidently more potent in antitumor activity compared with free etoposide, as confirmed by a cytotoxicity test using an MTT assay and an apoptosis test with fluorescence-activated cell sorter (FACS) analysis. These findings suggest that SCNs hold tremendous promise in the areas of controlled drug delivery and targeted cancer therapy.Keywords: strontium carbonate, nanoparticles, pH-sensitive drug delivery, etoposide, anticancer activity